The bases for differences in Na transport across epithelia (e.g. frog skin) in vitro and in vivo are being examined. The effect of a negatively charged layer external to the apical membrane may be substantial since it would modify the Na concentration through a Donnan effect. Detailed implications of such a system are being worked out. Further research will be carried out on membrane potential differences as well as the transepithelial potential difference across amphibian skins in vivo and under conditions that are natural for the animals. Fractionation of epithelial microsomes is directed toward isolation of the apical membrane systems responsible for Na and for Cl transport.